瘤微环境响应的基于DNA的纳米医学触发了用于增强免疫治疗的先天感应
Jinyang Li1, Xiaoyu Han1, Shanshan Gao1
1State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Journal of nanobiotechnology
|October 20, 2023
概括
通过纳米颗粒传递的双链DNA (dsDNA) 激活天生的免疫力,增强抗瘤反应并克服免疫疗法耐药性. 这种新的方法显示出显著的瘤生长抑制和组合治疗的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米医学是一种纳米医学.
- 在瘤学瘤学.
背景情况:
- 瘤微环境中的天生的免疫感知能力差,限制了免疫治疗的有效性.
- 双链DNA (dsDNA) 可以通过cGAS-STING通路激活先天免疫,但面临着传递和稳定性的挑战.
- 免疫刺激剂的有效输送对于增强抗瘤免疫力至关重要.
研究的目的:
- 开发一种对瘤微环境有反应性的纳米药物,以有效地传递dDNA.
- 研究dDNA载荷纳米粒子在增强抗瘤免疫疗法的潜力.
- 为了评估dsDNA纳米医学与检查点抑制剂的联合疗效.
主要方法:
- 构建载有dsDNA (dsDNA@DMONs) 的树突性半孔性有机纳米粒子 (DMONs).
- 对于诱导I型干扰素 (IFN-I) 生产的dsDNA@DMONs的体外和体内评估.
- 在小鼠黑色素瘤模型中评估免疫细胞激活 (树突细胞,T细胞) 和抗瘤功效.
- 用抗PD-L1抗体进行组合治疗的研究.
主要成果:
- dsDNA@DMONs在免疫和瘤细胞中有效诱导了显著的IFN-Is产生.
- 治疗促进了树突细胞成熟和T细胞激活,增强了先天性和适应性免疫反应.
- 单剂dsDNA@DMONs在B16-F10黑色素瘤模型中实现了51.0%的瘤生长抑制,具有良好的生物安全性.
- 与抗PD-L1联合治疗导致瘤几乎完全回归.
结论:
- 响应瘤微环境的dsDNA载入纳米医药是克服免疫疗法耐药性的有希望的策略.
- 开发的纳米药物通过促进IFN-Is的产生,有效地激活先天免疫力.
- 这种方法有可能重塑瘤微环境并提高治疗结果,特别是在组合疗法中.
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